We propose to characterize the MLR locus alleles in approximately 300 patients with Hodgkin's disease or cancer of the breast, lung, cervix, colon and prostate and to compare the frequency of these alleles to a normal population of approximately 100 persons who will be studied in the same way. The MLR genetic locus is located on Chromosome 6 in man and is part of the major histocompatibility complex. In mice, genes in the analogous H-2 complex are strongly associated with susceptibility to virally-induced leukemia and other forms of cancer. In man, dogs and Rhesus monkeys, the MLR locus is located at one end of this major histocompatibility complex, at a site rather distant from the serologically defined HL-A loci. It is in this region that the Ir genes controlling immune responsiveness to synthetic polymeric antigens have been placed in studies of Rhesus monkeys. It would appear then that unless entire haplotypes of this genetic region are involved in the genetics in cancer, studying the MLR locus would be the most appropriate area to seek a "cancer susceptibility gene(s)". Until recently, however, MLR locus typing has been logistically impractical because of the need for fresh blood from a large number of MLR homozygous donors for mixed leukocyte cultures. We have now established long-term lymphoblastoid cell lines on over twenty MLR homozygous typing donors; these lines can be used for MLR typing instead of fresh blood from each typing donor. The information gained by the proposed studies could have far-reaching effects in identifying "high cancer risk" genes, haplotypes, patients and families. It should also serve to enhance our understanding of the genetics of histocompatibility matching for organ transplantation.